The inventor has previously shown that CD200 (OX2) is a powerful immune suppressant and that administering CD200 could inhibit graft rejection and prevent fetal loss and auto immune disease (WO 99/24565, to the present inventor, Gorczynski et al. 1998, 1999a, 1999b, 2000). In particular, the inventor has previously shown that administering antibodies to CD200 inhibited the graft survival generally seen following pre-transplant pv immunization and that administering CD200 inhibits graft rejection. It has also been shown that there is a negative association between levels of CD200 and risk of fetal loss. In particular, administering CD200 reduced fetal loss rates while inhibiting CD200 reversed the effect. The inventor has also shown that administering CD200 prevents autoimmunity. Further, CD200 inhibits cytotoxic cells and IL-2 production and induces IL-4 production. In addition, CD200 is responsible for promoting tumor metastases and inhibiting CD200 reduces tumor cell growth. Recently, Hoek et al. (2000) prepared a CD200 knockout mouse and speculated the role for CD200 in the regulation of cells of the myeloid differentiation pathway and in inflammatory processes within the central nervous system. All of these results demonstrate that CD200 is involved in immune suppression.
The effects of CD200 were reinforced by simultaneous infusion of CD200 receptor (CD200r) bearing cells, and together these data indicate that CD200:CD200r interactions represented a novel immunoregulatory pathway molecule, which influenced the outcome of TCR:antigen encounter. This immunoregulation was presumed to represent a counter to the immunostimulatory pathways which are triggered after the delivery of costimulatory signals resulting from other ligand:coreceptor interactions, such as those of CD40L with CD40 and CD28 (and CTLA4) with CD80/CD86.
There may be a number of situations wherein it is desirable to inhibit the immune suppressive effects of CD200, for example when immune stimulation (and not suppression) is needed.